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Chemotaxis and Direction of Cell Migration

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Chemotaxis is the movement of cells in response to a chemical stimulus.

While chemoattractants direct cell movement along their concentration gradient, chemorepellents signal the cell to move away from the stimulus.

These chemical cues are usually small molecules such as peptides, sugars, and lipids, which can bind specific cell-surface receptors.

For example, the tripeptides released by bacteria, such as E.coli can bind and activate the G-protein coupled receptors or GPCRs on the surface of neutrophils.

The activated GPCRs polarize the cell by locally amplifying the signal via different signaling cascades — the Rac pathway at the cell front, and the Rho pathway at the cell rear.

This leads to cytoskeletal reorganization within the neutrophil that orients and directs its movement towards the pathogen.

In addition to diffusible chemicals, substrate-bound molecules, such as laminin glycoproteins, also induce chemotaxis.

These stimulants promote the adhesion of membrane protrusions to the substrate, thus directing cell migration along the chemical gradient.

Overview

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Cells can detect chemical cues in their environment and reorganize the cytoskeleton to migrate toward them or away from them. This directional migration, called chemotaxis, is essential during embryogenesis and development, immune response, tissue repair and regeneration, and reproduction. These chemical cues can either attract or repel the cell's movement. For example, axon development is determined by a combination of chemoattractants and chemorepellents that direct the growing axon towards the appropriate targets.

Sensing the Gradient

Cells exhibit chemotaxis across a chemical gradient by sensing the spatial difference in the chemical concentration between the two ends of the cell. Most eukaryotic cells can detect a difference of as little as 1 to 2 percent between the cell front and rear. Smaller cells, such as prokaryotes, cannot detect this spatial gradient because the distance between the front and rear of the cell is too small. Instead, they detect the gradient temporally by moving in random bouts and identifying the direction in which the chemical concentration increases. They then continue moving along that direction for a short distance before reverting to tumbling in random directions.

Chemotaxis in Cancer

Diseases involving abnormal cell migration usually exhibit abnormal functioning of cell surface receptors or unregulated expression of ligands for these receptors. During tumor metastasis, the presence of a specific receptor and its ligands determine the likely target organ for establishing secondary tumors. For example, the common secondary tumor sites in breast cancer patients are the lungs and bone marrow. The CXCR4 receptor found in breast cancer cells binds to the ligand SDF-1α, which is expressed in lung and bone marrow tissue. This ligand triggers directional migration of the metastatic cells towards these organs, thus establishing secondary tumors.

Transcript

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Chemical Gradient

Directional Migration

Chemoattractants

Chemorepellents

Cell Surface Receptors

Tumor Metastasis